Sociodemographic disparities in sodium-glucose cotransporter-2 inhibitor use among US kidney transplant recipients: An observational study of real-world pharmacy records.

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

Statins in Kidney Transplant Recipients: Usage, All-Cause Mortality, and Interactions with Maintenance Immunosuppressive Agents.

SIGNIFICANCE STATEMENT: Cardiovascular diseases account for 32% of deaths among kidney transplant recipients. Statin therapy is common in this population. However, its effect on mortality prevention remains unclear among kidney transplant recipients, whose clinical risk profile might be unique because of concomitant immunosuppressive therapy. In this national study of 58,264 single-kidney transplant recipients, statin use was associated with a 5% decrease in mortality. More importantly, this protective association was stronger among those who used a mammalian target of rapamycin (mTOR) inhibitor for immunosuppression (27% decrease in mTOR inhibitor users versus 5% in nonusers). Our results suggest that statin therapy may reduce mortality in kidney transplant recipients and that the strength of this protective association may vary by immunosuppression regimen. BACKGROUND: Cardiovascular diseases are the leading cause of mortality in kidney transplant (KT) recipients, accounting for 32% of deaths. Statins are widely used in KT recipients, but effectiveness for preventing mortality remains unclear in this population, especially because of interaction between statins and immunosuppressive agents. We analyzed a national cohort to assess the real-world effectiveness of statins for reducing all-cause mortality in KT recipients. METHODS: We studied statin use and mortality among 58,264 adults (18 years or older) who received single kidneys between 2006 and 2016 and had Medicare part A/B/D. Statin use was ascertained from Medicare prescription drug claims and deaths from Center for Medicare and Medicaid Services records. We estimated the association of statin use with mortality using multivariable Cox models, with statin use as a time-varying exposure and immunosuppression regimen as effect modifiers. RESULTS: Statin use increased from 45.5% at KT to 58.2% at 1-year post-KT to 70.9% at 5-year post-KT. We observed 9785 deaths over 236,944 person-years. Overall, statin use was significantly associated with lower mortality (adjusted hazard ratio [aHR], 0.95; 95% confidence interval [CI], 0.90 to 0.99). The strength of this protective association varied by calcineurin inhibitor use (among tacrolimus users, aHR, 0.97; 95% CI, 0.92 to 1.03 versus among calcineurin nonusers, aHR, 0.72; 95% CI, 0.60 to 0.87; interaction P =0.002), mammalian target of rapamycin (mTOR) inhibitor use (among mTOR inhibitor users, aHR, 0.73; 95% CI, 0.57 to 0.92 versus among nonusers, aHR, 0.95; 95% CI, 0.91 to 1.00; interaction P =0.03), and mycophenolate use (among mycophenolate users, aHR, 0.96; 95% CI, 0.91 to 1.02 versus among nonusers, aHR, 0.76; 95% CI, 0.64 to 0.89; interaction P =0.002). CONCLUSION: Real-world evidence supports statin therapy for reducing all-cause mortality in KT recipients. Effectiveness might be greater when combined with mTOR inhibitor-based immunosuppression.

Psychosocial assessment tools for children and young people aged 5-18 years: A rapid review of the literature.

AIM: Schools are a key platform for health promotion and a point of connection to local health-care services, with an almost universal reach across the child and adolescent population. This study sought to determine whether validated psychosocial assessment tools exist for a school-based nursing program that would assist in providing an initial health assessment to identify and understand the needs of children and young people referred to the nurse, with the outcome of appropriate connection to external health and wellbeing services. METHODS: Rapid evidence assessment methodology was utilised to identify validated tools that could identify psychosocial concerns in children and young people aged 5-18 years. We identified articles from peer-reviewed journals via three electronic bibliographic databases (PubMed, Embase and CINAHL). We then extended the search for evidence through a search of the grey literature. RESULTS: From 3963 peer-reviewed articles found in the database search, 10 relevant peer-reviewed publications met inclusion criteria. In combination with 12 grey literature sources, 33 tools were identified. These included self-report tools (typically for children aged 11 years and older), parent-report and teacher-report tools. We identified the six most promising psychosocial assessment tools. However, there was limited description about implementation within school-based nursing programs. CONCLUSIONS: Several tools exist that show promise in assisting school-based nursing programs to conduct preliminary psychosocial assessments for children and young people. The introduction of any tools into practice would require implementation guidance and evaluation, including how and when they should be used, and when referral and follow-up is required.

Real-World Effectiveness of Remdesivir in Adults Hospitalized With Coronavirus Disease 2019 (COVID-19): A Retrospective, Multicenter Comparative Effectiveness Study.

BACKGROUND: There is an urgent need to understand the real-world effectiveness of remdesivir in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This was a retrospective comparative effectiveness study. Individuals hospitalized in a large private healthcare network in the United States from 23 February 2020 through 11 February 2021 with a positive test for SARS-CoV-2 and ICD-10 diagnosis codes consistent with symptomatic coronavirus disease 2019 (COVID-19) were included. Remdesivir recipients were matched to controls using time-dependent propensity scores. The primary outcome was time to improvement with a secondary outcome of time to death. RESULTS: Of 96 859 COVID-19 patients, 42 473 (43.9%) received at least 1 remdesivir dose. The median age of remdesivir recipients was 65 years, 23 701 (55.8%) were male, and 22 819 (53.7%) were non-White. Matches were found for 18 328 patients (43.2%). Remdesivir recipients were significantly more likely to achieve clinical improvement by 28 days (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI], 1.16-1.22). Remdesivir patients on no oxygen (aHR 1.30, 95% CI, 1.22-1.38) or low-flow oxygen (aHR 1.23, 95% CI, 1.19-1.27) were significantly more likely to achieve clinical improvement by 28 days. There was no significant impact on the likelihood of mortality overall (aHR 1.02, 95% CI, .97-1.08). Remdesivir recipients on low-flow oxygen were significantly less likely to die than controls (aHR 0.85, 95% CI, .77-.92; 28-day mortality 8.4% [865 deaths] for remdesivir patients, 12.5% [1334 deaths] for controls). CONCLUSIONS: These results support the use of remdesivir for hospitalized COVID-19 patients on no or low-flow oxygen. Routine initiation of remdesivir in more severely ill patients is unlikely to be beneficial.

Use of Hydroxychloroquine, Remdesivir, and Dexamethasone Among Adults Hospitalized With COVID-19 in the United States : A Retrospective Cohort Study.

BACKGROUND: Relatively little is known about the use patterns of potential pharmacologic treatments of COVID-19 in the United States. OBJECTIVE: To use the National COVID Cohort Collaborative (N3C), a large, multicenter, longitudinal cohort, to characterize the use of hydroxychloroquine, remdesivir, and dexamethasone, overall as well as across individuals, health systems, and time. DESIGN: Retrospective cohort study. SETTING: 43 health systems in the United States. PARTICIPANTS: 137 870 adults hospitalized with COVID-19 between 1 February 2020 and 28 February 2021. MEASUREMENTS: Inpatient use of hydroxychloroquine, remdesivir, or dexamethasone. RESULTS: Among 137 870 persons hospitalized with confirmed or suspected COVID-19, 8754 (6.3%) received hydroxychloroquine, 29 272 (21.2%) remdesivir, and 53 909 (39.1%) dexamethasone during the study period. Since the release of results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in mid-June, approximately 78% to 84% of people who have had invasive mechanical ventilation have received dexamethasone or other glucocorticoids. The use of hydroxychloroquine increased during March 2020, peaking at 42%, and started declining by April 2020. By contrast, remdesivir and dexamethasone use gradually increased over the study period. Dexamethasone and remdesivir use varied substantially across health centers (intraclass correlation coefficient, 14.2% for dexamethasone and 84.6% for remdesivir). LIMITATION: Because most N3C data contributors are academic medical centers, findings may not reflect the experience of community hospitals. CONCLUSION: Dexamethasone, an evidence-based treatment of COVID-19, may be underused among persons who are mechanically ventilated. The use of remdesivir and dexamethasone varied across health systems, suggesting variation in patient case mix, drug access, treatment protocols, and quality of care. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; and National Institute on Aging.

Alpha-1 Antitrypsin Deficiency-Associated Clinical Manifestations and Healthcare Resource Use in the United States.

Pulmonary events (PEs) associated with alpha-1 antitrypsin deficiency (AATD) can have a severe clinical course and increase healthcare resource use (HRU). However, AATD-associated HRU and healthcare costs have not been extensively described. This study describes and compares real-world HRU and healthcare costs among US patients with severe (requiring hospitalization after AATD-related PE) versus nonsevere AATD clinical course. Administrative healthcare claims for patients with a second primary AATD diagnosis between 6/1/2008 and 12/31/2017 were analyzed from 2 databases (requiring continuous enrollment 6 months preceding diagnosis). Patient baseline characteristics and AATD-associated PE incidence rates, HRU, and healthcare costs during follow-up were compared in patients with severe versus nonsevere AATD. Of 5109 patients with a second AATD diagnosis, 2674 (severe, n = 711 [26.6%]; nonsevere, n = 1963 [73.4%]) had ≥1 AATD-associated PE. PE incidence per 100 person-years was higher in patients with severe versus nonsevere AATD. Annual incidences (mean ± SD) of emergency department (1.2 ± 5.7 vs. 0.4 ± 1.2), inpatient (1.3 ± 2.5 vs. 0.1 ± 0.5), and outpatient (10.3 ± 15.9 vs. 5.7 ± 13.2) visits were higher in patients with severe versus nonsevere AATD. Median (interquartile range) annual costs were also higher for patients with severe versus nonsevere AATD for emergency department ($185 [$0-$1665] vs. $0 [$0-$264]), inpatient ($16,038 [$2968-$70,941] vs. $0 [$0-$0]), and outpatient ($2663 [$412-$10,277] vs. $1114 [$134-$4195]) visits. Higher percentages of patients with severe AATD were prescribed augmentation therapy, antibiotics, or corticosteroids. These findings suggest that patients with severe AATD have higher incidence of AATD-associated PEs, as well as higher HRU and healthcare costs.

Does the Use of a Pulmonary Artery Catheter Make a Difference During or After Cardiac Surgery?

Pulmonary artery catheters (PACs) were introduced in 1970. Since then, their use has steadily increased. However, there have been questions raised regarding their efficacy for multiple clinical scenarios. The purpose of this systematic review was to determine the safety and effectiveness of routine use of PACs post cardiac surgery on mortality, complications, days in intensive care unit, days in hospital, and costs in patients undergoing cardiac surgery, or patients who end up in an intensive care unit. METHODS: Medline, All EBM, EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched using predetermined search terms. Google, British Medical Journal (BMJ) Best Practice, and the National Institute for Clinical Excellence (NICE) were also searched. All searches were from 2012 to current to update a previous review from 2013. Studies were included if they involved adult cardiac surgery patients, or intensive care unit (ICU) patients requiring haemodynamic monitoring. All other surgical patients were excluded. RESULTS: Six articles were included in this review. Of the six articles, five were randomised or observational studies, and one was an expert recommendation. For all cardiac surgery patients and patients having coronary artery bypass grafting, there was no difference in mortality. There was an increase in mortality in high-risk cardiac surgery patients, who had a PAC. For patients following coronary artery bypass grafting, there was no difference in ICU length of stay (LOS) but for patients following cardiac surgery total length of hospital stay >30days was greater in patients with a PAC. For patients following coronary artery bypass grafting, in-hospital costs for the entire hospitalisation were higher in patients with a PAC and, there was no difference in complications between PAC and a central venous catheter use. Overall, PACs were not a predictor of worse outcomes. CONCLUSION: This review revealed that PAC use was associated with a poorer outcome in a small subset of cardiac surgical patients but in the majority of patients PAC use made no difference to outcome. Further studies are required to confirm the true safety and efficacy of PAC use in cardiac surgery.

Adding an accredited exercise physiologist role to a new model of care at a secure extended care mental health service: a qualitative study.

BACKGROUND: Accredited exercise physiologists (AEPs) are emerging as essential members of allied health in the management of non-communicable chronic diseases. People diagnosed with severe mental illness (SMI) are at greater risk of cardiovascular diseases. Secure extended care units (SECUs) provide treatment, supervision and support for people with SMI whose needs cannot be met adequately in the community. However, the role of AEPs in SECUs has not been described. AIM: Describe the processes and outcomes of adding an AEP to a new model of care at a SECU. METHODS: An exploratory study with emphasis on qualitative data. Interviews with a purposive sample of SECU staff. RESULTS: Participants articulated concern about poor physical health of which two themes emerged (1) the development of the AEP role; a calculated gamble and (2) the practical application of the role. CONCLUSIONS: An AEP was identified as the role to best implement the organisations vision to improve physical health of people with SMI. Implementation and practical application of the role relied on an informed calculated gamble. Yet, once embedded in the service, the AEP role was able to capacity build among clinical staff, develop a treatment pathway, and implement consumer specific physical health interventions.

Patient satisfaction of telephone or video interpreter services compared with in-person services: a systematic review.

Objective This review was conducted to identify and synthesise the evidence around the use of telephone and video interpreter services compared with in-person services in healthcare. Methods A systematic search of articles published in the English language was conducted using PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Database of Abstracts of Reviews of Effects (DARE), Joanna Briggs, Google Scholar and Google. Search terms included 'interpreter', 'patient satisfaction', 'consumer satisfaction' and 'client satisfaction'. Any study that did not compare in-person interpreter services with either telephone or video interpreter services was excluded from analysis. Studies were screened for inclusion or exclusion by two reviewers, using criteria established a priori. Data were extracted via a custom form and synthesised. Results The database search yielded 196 studies, eight of which were included in the present review. The search using an Internet search engine did not identify any relevant studies. Of the studies included, five used telephone and three used video interpreter services. All studies, except one, compared levels of satisfaction regarding in-person interpretation and telephone or video interpretation. One study compared satisfaction of two versions of video interpretation. There is evidence of higher satisfaction with hospital-trained interpreters compared with ad hoc (friend or family) or telephone interpreters. There is no difference in satisfaction between in-person interpreting, telephone interpreting or interpretation provided by the treating bilingual physician. Video interpreting has the same satisfaction as in-person interpreting, regardless of whether the patient and the physician are in the same room. Higher levels of satisfaction were reported for trained telephone interpreters than for in-person interpreters or an external telephone interpreter service. Conclusions Current evidence does not suggest there is one particular mode of interpreting that is superior to all others. This review is limited in its translational capacity given that most studies were from the US and in a Spanish-speaking cohort. What is known about the topic? Access to interpreters has been shown to positively affect patients who are not proficient in speaking the local language of the health service. What does this paper add? This paper adds to the literature by providing a comprehensive summary of patient satisfaction when engaging several different types of language interpreting services used in healthcare. What are the implications for practitioners? This review provides clear information for health services on the use of language interpreter services and patient satisfaction. The current body of evidence does not indicate a superior interpreting method when patient satisfaction is concerned.

Informing best practice for conducting morbidity and mortality reviews: a literature review.

Objective Preventable hospital mortality is a critical public health issue, particularly when mortalities are associated with events that are preventable. Mortality and morbidity reviews (MMRs) provide a rigorous, systematic, open, collaborative and transparent review process for clinicians to examine areas of improvement. The aim of the present review was to explore the evidence for best practice when conducting MMRs. Methods Searches of published and grey literature from 2009 to February 2016 were conducted. This period was selected to update a previous review. Inclusion and exclusion criteria was established a priori and based on the Population-Intervention-Comparison-Outcome (PICO) framework. Specific search terms were generated and used to identify relevant articles, with reference lists and citing articles also screened for inclusions. Titles and abstracts were screened and duplicates removed. Study details regarding setting, study design, reported outcomes, tool type, clinicians present and the timing of MMRs were extracted and summarised. Results After screening, 31 documents were included in the present review: 20 peer-reviewed articles and 11 items from the grey literature. Specific outcomes reported included mortality rates, satisfaction, education, cost and quality of care. The most common features of MMRs included timing, leadership, attendees, case presentation format, terms of reference, agenda and governance. Conclusions MMRs decrease gross mortality rates and are effective in identifying and engaging clinicians in system improvements. MMRs should not focus on the actions of individuals, rather on education and/or quality improvement. MMRs should consist of a multidisciplinary team following a structured presentation format with an analysis of error process including actions to be followed-up. Further, it is possible for a single standardised MMR to be implemented hospital wide. What is known about the topic? MMRs are conducted in a variety of clinical settings to educate clinicians and improve patient care. What does this paper add? This review updates a previous review published in 2009 and summarises current evidence around morbidity and mortality reviews. This review also provides a framework for a standardised MMR to be implemented hospital wide. What are the implications for practitioners? This summary of the evidence can be used to guide the development, formation or conduct of MMRs in any healthcare setting.

Benefits of whole-body vibration to people with COPD: a community-based efficacy trial.

BACKGROUND: Benefits of community-based whole-body vibration (WBV) as a mode of exercise training for people with chronic obstructive pulmonary disease (COPD) have not been investigated. The low skill demand of WBV may enhance habitual sustainability to physical activity by people with COPD, provided efficacy of WBV can be established. The purpose of this trial was to compare a community-based WBV intervention with a sham WBV (SWBV) intervention and monitor exacerbations, exercise tolerance, and functional performance of the lower limbs of people with COPD. METHODS: Community-dwelling adults with a GOLD clinical diagnosis of COPD were recruited to the trial. This was a Phase II efficacy trial with crossover to sham intervention interspersed with two-week washout. Each six-week intervention consisted of two sessions per week of either WBV or SWBV. The interventions were completed in the home of each participant under supervision. The outcome measures were selected psychological (perceived dyspnoea) and physiological (heart rate and oxygen saturation) responses to exercise, simulated activities of daily living (timed-up-and got test and 5-chair stands test), and selected kinematic variables of gait across the 14-week trial. RESULTS: Sixteen adults with stable COPD were recruited to the trial. No exacerbations were reported during the WBV or SWBV interventions. After WBV, performance of activities of daily living (ADLs) and gait improved (p ≤ 0.05), while there was no change after SWBV (p > 0.05). Despite five withdrawals during the washout period, a 100% compliance to each six-week intervention was noted. CONCLUSIONS: Results showed that WBV did not exacerbate symptoms of COPD that can be associated with physical inactivity. The WBV intervention improved tests to simulate ADLs such as rising from a chair, turning, and walking gait with greater effect than a SWBV intervention. If a placebo effect was systemic to the WBV intervention, the effect was negligible. As a standalone community-based intervention, WBV was an efficacious mode of exercise training for people with stable COPD that did not negatively effect exercise tolerance or exacerbate the disease, while concurrently improving functional performance of the lower limbs. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12612000508875.

Musculoskeletal stiffness during hopping and running does not change following downhill backwards walking.

Eccentric contractions that provide spring energy can also cause muscle damage. The aim of this study was to explore leg and vertical stiffness following muscle damage induced by an eccentric exercise protocol. Twenty active males completed 60 minutes of backward-walking on a treadmill at 0.67 m/s and a gradient of - 8.5° to induce muscle damage. Tests were performed immediately before; immediately post; and 24, 48, and 168 hours post eccentric exercise. Tests included running at 3.35 m/s and hopping at 2.2 Hz using single- and double-legged actions. Leg and vertical stiffness were measured from kinetic and kinematic data, and electromyography (EMG) of five muscles of the preferred limb were recorded during hopping. Increases in pain scores (over 37%) occurred post-exercise and 24 and 48 hours later (p < 0.001). A 7% decrease in maximal voluntary contraction occurred immediately post-exercise (p = 0.019). Changes in knee kinematics during single-legged hopping were observed 168 hours post (p < 0.05). No significant changes were observed in EMG, creatine kinase activity, leg, or vertical stiffness. Results indicate that knee mechanics may be altered to maintain consistent levels of leg and vertical stiffness when eccentric exercise-induced muscle damage is present in the lower legs.

The interday reliability of ankle, knee, leg, and vertical musculoskeletal stiffness during hopping and overground running.

A number of methods are used to measure lower extremity musculoskeletal stiffness, but there is a paucity of research examining the reliability of these techniques. Therefore, we investigated the reliability of vertical, leg, knee, and ankle stiffness during overground running and hopping in 20 active men. Participants were required to run on a 10 m overground runway at 3.83 m/s (actual; 3.35 ± 0.12 m/s) and to hop in place at 2.2 Hz (actual; 2.37 ± 0.03 Hz), and at a self-selected frequency (actual; 2.05 ± 0.12 Hz) and at 2.2 Hz (actual; 2.39 ± 0.04 Hz). Reliability was determined using the intraclass correlation coefficient, coefficient of variation, mean differences, and Cohen's effect sizes. There was good reliability for vertical stiffness, moderate reliability for leg stiffness, and poor reliability for knee and ankle stiffness during the running task. Similar results were observed during the 2.2 Hz hopping tasks, with good reliability displayed for vertical stiffness and poor reliability for ankle and knee stiffness. In conclusion, our results suggest that vertical stiffness is a reliable measure when running at 3.83 m/s and hopping at 2.2 Hz.

Agreement between force and deceleration measures during backward somersault landings.

This study examined the agreement between force platform and inertial measurement unit (IMU) measures of backward somersault landings. Seven female gymnasts performed three trials, taking off from a 90 cm vaulting box and using competition landing technique. Two force platforms (1000 Hz) covered with a 6.4 cm thick carpeted landing surface measured the ground reaction forces. One inertial measurement unit (500 Hz) fixed on the second thoracic vertebra measured peak resultant deceleration of the gymnast. Measurement agreement between vertical and resultant peak force measures, and resultant peak force and peak deceleration was assessed using mean differences, Pearson's correlation, and Cohen's effect size (ES) statistics. There was perfect measurement agreement between vertical and resultant peak forces (R = 1.0, p < 0.001; ES = 0.005), but only moderate measurement agreement between resultant peak force and peak resultant deceleration (Mean Difference = -2.16%, R = 0.4, p = ns; ES = 0.121). Backward somersault landings can be assessed using either uni-axial or tri-axial force platforms to measure ground impact load/force, as the landing movements are almost purely vertical. However, force measures are not the same as peak resultant decelerations from IMUs which give an indication of impact shock. Landing load/shock measures are potentially important for injury prevention.

Incidence of Statin-Associated Adverse Events in Kidney Transplant Recipients.

BACKGROUND: Statins are the third most prescribed drug class in kidney transplant recipients as cardiovascular diseases is the leading cause of death in this population. However, statins' safety profile remains unclear in kidney transplant recipients who are uniquely burdened by concomitant immunosuppression and comorbidities. We conducted a national study to characterize the association of statin use with adverse events in kidney transplant recipients. METHODS: We studied adult (≥18) single-organ kidney transplant recipients in 2006-2016 with Medicare as primary payer (n=57,699). We used prescription drug claims to capture statin use, and ICD-9/10 diagnosis codes to capture statin-related adverse events (post-transplant diabetes mellitus, hemorrhagic stroke, cataract, liver injury, and rhabdomyolysis). We conducted multivariable Cox regression for each outcome with statin use as a time-varying exposure. RESULTS: Post-transplant diabetes mellitus was the most common outcome (5-year Kaplan-Meier incidence; 43% in statin users vs. 35% in non-users), followed by cataract (22% vs. 12%), liver injury (2% vs. 3%), hemorrhagic stroke (1.9% vs. 1.4%), and rhabdomyolysis (1.5% vs. 0.9%). In our multivariable analysis, statin use was associated with higher hazard of post-transplant diabetes mellitus (aHR=1.12 [95% CI, 1.07-1.18]), cataract (aHR=1.22 [1.14-1.31]), and rhabdomyolysis (aHR=1.37 [1.10-1.71]), but lower hazard of liver injury (aHR=0.82 [0.71-0.95]). Statin use was not associated with hemorrhagic stroke (aHR=1.04 [0.86-1.26]). CONCLUSIONS: Statins appear to be generally well-tolerated in kidney transplant recipients. However, statin use might be associated with slightly higher risk of post-transplant diabetes mellitus, cataract, and rhabdomyolysis.

Gabapentin, Concomitant Prescription of Opioids, and Benzodiazepines among Kidney Transplant Recipients.

BACKGROUND: Gabapentinoids, commonly used for treating neuropathic pain, may be misused and coprescribed with opioid and benzodiazepine, increasing the risk of mortality and dependency among kidney transplant recipients. METHODS: We identified adult kidney transplant recipients who enrolled in Medicare Part D in 2006-2017 using the United States Renal Data System/Medicare claims database. We characterized recipients' post-transplant concomitant prescription of gabapentinoids, opioids, and benzodiazepine stratified by transplant year and recipient factors (age, sex, race, and diabetes). We investigated whether concomitant prescriptions were associated with postkidney transplant mortality using Cox regression. Models incorporated inverse probability weighting to adjust for confounders. RESULTS: Among 63,359 eligible recipients, 13% of recipients filled at least one gabapentinoid prescription within 1 year after kidney transplant. The prevalence of gabapentinoid prescriptions increased by 70% over the study period (16% in 2017 versus 10% in 2006). Compared with nonusers, gabapentinoids users were more likely to have diabetes (55% versus 37%) and obesity (46% versus 34%). Of the 8509 recipients with gabapentinoid prescriptions, 45% were coprescribed opioids, 7% were coprescribed benzodiazepines, and 3% were coprescribed both opioids and benzodiazepines. Compared with no study prescriptions, gabapentinoid monotherapy (adjusted hazard ratio [aHR]=1.25; 95% confidence interval [CI], 1.16 to 1.32) and combination therapy (gabapentinoids and opioids [aHR=1.49; 95% CI, 1.39 to 1.60], gabapentinoids and benzodiazepines [aHR=1.46; 95% CI, 1.03 to 2.08], and coprescribing all three [aHR=1.88; 95% CI, 1.18 to 2.98]) were all associated with a higher risk of postkidney transplant mortality. CONCLUSIONS: Gabapentinoid coprescription with both benzodiazepines and opioids among kidney transplant recipients increased over time. Kidney transplant recipients prescribed gabapentinoids had a higher risk of post-transplant mortality, and the risk was higher with opioids or benzodiazepine coprescription.

Gait classification in a population of adults with hereditary spastic paresis.

BACKGROUND: Classification of gait in adults with hereditary spastic paresis is limited. Our aim was to use a previously established system to classify gait. METHODS: Forty-nine participants were retrospectively recruited and grouped into existing classifications based on sagittal plane knee joint kinematic data extracted from a 3D analysis. Waveform analysis was used to compare the grouped data to determine if and where differences in the subjective classifications appeared. FINDINGS: Classification of gait patterns in adults with hereditary spastic paresis is successful. Differences between groups in line with the classification system were confirmed by statistical analysis. Crouch gait is illustrated by a flexed knee throughout stance phase. Recurvatum gait is dominated by knee hyperextension in mid-late stance. Stiff-knee gait demonstrates limited knee range of motion in stance and jump-knee gait is characterised by less knee flexion in early and mid-stance phase than all groups. Sagittal plane hip and ankle kinematics compliment group differences at the knee joint. The jump-knee group is more flexed at the hip than all groups during loading response phase and mid-stance; and the recurvatum group is more extended at the hip than the crouch, jump-knee, and stiff-knee groups during mid and late-stance phase. There is less ankle dorsiflexion throughout stance phase in the recurvatum group than in all other groups. INTERPRETATION: Sagittal plane knee joint kinematic data can be subjectively used to classify gait features in adults with hereditary spastic paresis. Novel analysis show hip and ankle sagittal plane kinematics can be used to further assist classification.

Thromboprophylaxis in people hospitalized with COVID-19: Assessing intermediate or standard doses in a retrospective cohort study.

Background and Objectives: Current clinical guidelines recommend thromboprophylaxis for adults hospitalized with coronavirus disease 2019 (COVID-19), yet it is unknown whether higher doses of thromboprophylaxis offer benefits beyond standard doses. Methods: We studied electronic health records from 50 091 adults hospitalized with COVID-19 in the United States between February 2020 and February 2021. We compared standard (enoxaparin 30 or 40 mg/day, fondaparinux 2.5 mg, or heparin 5000 units twice or thrice per day) versus intermediate (enoxaparin 30 or 40 mg twice daily, or up to 1.2 mg/kg of body weight daily, heparin 7500 units thrice per day or heparin 10 000 units twice or thrice per day) thromboprophylaxis. We separately examined risk of escalation to therapeutic anticoagulation, severe disease (first occurrence of high-flow nasal cannula, noninvasive positive pressure ventilation or invasive mechanical ventilation), and death. To summarize risk, we present hazard ratios (HRs) with 95% confidence intervals (CIs) using adjusted time-dependent Cox proportional hazards regression models. Results: People whose first dose was high intensity were younger, more often obese, and had greater oxygen support requirements. Intermediate dose thromboprophylaxis was associated with increased risk of therapeutic anticoagulation (HR, 3.39; 95% CI, 3.22-3.57), severe disease (HR, 1.22; 95% CI, 1.17-1.28), and death (HR, 1.37; 95% CI, 1.21-1.55). Increased risks associated with intermediate-dose thromboprophylaxis persisted in subgroup and sensitivity analyses varying populations and definitions of exposures, outcomes, and covariates. Conclusions: Our findings do not support routine use of intermediate-dose thromboprophylaxis to prevent clinical worsening, severe disease, or death among adults hospitalized with COVID-19.

Patient-reported burden of dry eye disease in the UK: a cross-sectional web-based survey.

OBJECTIVES: To compare sociodemographics and vision-related quality of life (QoL) of individuals with or without dry eye disease (DED); and to explore the impact of DED symptom severity on visual function, activity limitations and work productivity. DESIGN: Cross-sectional web-based survey. SETTING: General UK population. PARTICIPANTS: Adults ≥18 years with (N=1002) or without (N=1003) self-reported DED recruited through email and screened. MAIN OUTCOME MEASURES: All participants completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), with six additional questions (items A3-A8), and the EuroQol 5 dimensions 5 levels. DED participants also completed Impact of Dry Eye on Everyday Life questionnaire, 5-item Dry Eye Questionnaire and the Standardised Patient Evaluation of Eye Dryness questionnaire along with the Ocular Comfort Index, Work Productivity and Activity Impairment and the Eye Dryness Score (EDS), a Visual Analogue Scale. RESULTS: Baseline demographic and clinical characteristics were similar in participants with versus without DED (mean age, 55.2 vs 55.0 years; 61.8% vs 61.0% women, respectively) based on recruitment targets. Scores were derived from NEI VFQ-25 using the new 28-item revised VFQ (VFQ-28R) scoring. Mean (SD) VFQ-28R scores were lower in participants with versus without DED, indicating worse functioning (activity limitations, 73.3 (12.3) vs 84.4 (12.3); socioemotional functioning, 75.3 (21.5) vs 90.3 (16.2); total score, 71.6 (12.8) vs 83.6 (12.6)). Higher percentages of problems/inability to do activities were observed among those with versus without DED. The impact of DED on visual function was worse for participants with more severe DED symptoms, as assessed by EDS. In addition, a higher EDS was associated with worse symptoms on common DED scales and a worse impact on work productivity. CONCLUSIONS: DED symptoms were associated with negative effects on visual function, activities and work productivity, whereas worse DED symptoms had a greater impact on vision-related QoL and work productivity.

Patient-Reported Burden of Dry Eye Disease in the United States: Results of an Online Cross-Sectional Survey.

PURPOSE: To evaluate functional vision, general health status, and work productivity in individuals with and without dry eye disease (DED). DESIGN: Cross-sectional study. METHODS: Setting: General US population (2018). STUDY POPULATION: Adults ≥18 years with (n = 1003) or without (n = 1006) self-reported DED. MAIN OUTCOME MEASURES: All respondents completed the National Eye Institute Visual Function Questionnaire (VFQ) and the EuroQol 5-dimensions 5-levels (EQ-5D-5L). All respondents with DED completed the eye dryness score (EDS) visual analogue scale, Ocular Comfort Index (OCI), and Work Productivity and Activity Impairment (WPAI) questionnaire. Half of respondents with DED completed the Impact of Dry Eye on Everyday Life (IDEEL) questionnaire; the other half completed the Dry Eye Questionnaire 5 (DEQ-5) and Standardized Patient Evaluation of Eye Dryness (SPEED), McMonnies, and Symptom Assessment in Dry Eye (SANDE) questionnaires. All analyses were descriptive. RESULTS: Respondents with DED reported more comorbidities, greater exposure to adverse environmental conditions, and lower (worse) mean (standard deviation) scores on the modified Rasch-scored 28-item VFQ (VFQ-28R) total score (68.8 [11.9] vs 81.2 [12.7]) and EQ-5D-5L (0.82 [0.13] vs 0.88 [0.14]) than respondents without DED. Respondents with DED and EDS ≥60 (highest discomfort) fared worse on OCI, VFQ-28R, and WPAI than respondents with DED and EDS <40 (lowest discomfort). Similar findings were observed with IDEEL, DEQ-5, SPEED, McMonnies, and SANDE scores. CONCLUSIONS: There is a substantial burden of DED on functional vision, general health status, and productivity; and further, these parameters appear to worsen with increasing EDS.